tetragastrin and 1-amino-3-(phosphonomethylene)cyclobutane-1-carboxylic-acid

The highly rigid and conformationally extended 2-amino-4-phosphonobutanoic acid (AP4) analogue (RS)-1-amino-3-(phosphonomethylene)-cyclobutane-1-carboxylic acid (cyclobutylene AP5) was synthesized and found to inhibit evoked responses in the rat lateral perforant path (LPP) with an IC50 of 41 (+/- 1.5 S.E.M.) microM and the medial perforant pathway with an IC50 of 218 (+/- 3.7 S.E.M.) microM. Furthermore, paired pulse potentiation experiments suggest that cyclobutylene AP5 acts, in part, at a presynaptic site in the LPP. Thus, cyclobutylene AP5 appears to act in a similar manner to L-AP4 in the perforant pathway. These data support the hypothesis that L-AP4 assumes an extended conformation at the L-AP4 receptor of the LPP.

Topics: Animals; Cyclobutanes; Dose-Response Relationship, Drug; Evoked Potentials; Hippocampus; In Vitro Techniques; Male; Molecular Conformation; Neural Pathways; Organophosphorus Compounds; Osmolar Concentration; Rats; Rats, Inbred Strains; Tetragastrin